The interactions between HIV-1 and its receptors are an important part of understanding the basic biology of the virus and, subsequently, understanding how the virus is controlled. Although the cellular receptors for HIV-1 have been characterized, the exact nature of the interaction of HIV-1 with the outer cell membrane leaflet during entry is not well understood. Fully characterizing HIV-host membrane interactions is critical to fully understanding the mechanisms of HIV-1 entry into host cells. Lipid rafts, cell membrane regions rich in sphingolipids and cholesterol, seem to aggregate as a result of HIV-1 binding to the host cell and possibly play an integral role in how the virus interacts with its receptors. The hypothesis of this proposal is that the chemokine receptor, CCR5, is localized to these specialized regions, and this localization may allow for primary selection for M-tropic infectivity due to more efficient virus entry. In order to determine the importance of lipid rafts for HIV-1 entry into host cells, I will utilize immunology techniques such as immunoblotting,flow cytometry, dot-blotting, immunoprecipitation and immunofluorescence. I will also utilize cell and molecular biology techniques such as palmitoylation studies; cell culture, and the generation of mutant cells. The studies completed in this proposal should provide new insights into mechanisms of interaction between HIV-1 and the host cell membrane during entry of the virus.